Our results showed that: (1) Blockade of calpain by non-selective calpain inhibitor MDL-28170 prevented convulsant stimulation induced KCC2 downregulation, and reduced the incidence and the severity of pentylenetetrazole (PTZ) induced seizures.
Gene and protein expression of NKCC1, KCC2 and KCC2 phosphorylated serine (KCC2 ser) 940 were measured 1 h post seizure termination and on PND 15 using RT- PCR and western blot.
Mice that lack both KCC2 isoforms die at birth due to severe motor defects, including disrupted respiratory rhythm, whereas mice with a targeted disruption of the first exon of KCC2b survive for up to 2 weeks but eventually die due to spontaneous seizures.
Repeated induction of seizures caused a decrease in KCC2 protein content in the inferior colliculus and hippocampus and an increase in the pons-medulla.
Our previous work demonstrates that prenatal stress with betamethasone-induced alterations to the expression of the K<sup>+</sup>/Cl<sup>-</sup> co-transporter (KCC2) in gamma-aminobutyric acid (GABA) interneurons lowers the seizure threshold in exposed animals.
Impairment of Cl<sup>-</sup> extrusion after KCC2 dysfunction has been involved in many central nervous system disorders, such as seizures, neuropathic pain, or spasticity, after a spinal cord injury (SCI).